Calcium (Ca2+) is a ubiquitous intracellular signal transducer, responsible for controlling numerous cellular processes. It regulates muscle contraction, neurotransmitter release, hormone secretion, cell motility, cell mitosis, and gene expression. Ca2+-signaling is employed throughout the life of the organism, beginning with a surge of Ca2+ at fertilization and ending with the induction of apoptosis, thereby, at cell death. Calcium is deeply involved in the cell proliferation. Several drugs that block Ca2+ entry into the cell, retard the cell growth in human melanoma, lung and colon carcinoma, and prostate cancer [See, e.g., Haverstick, D. M. et al.: Cancer Res. 60 (2000) 1002-8].
There are many proteins involved in the compound role of calcium in the organism having high-affinity or low-affinity Ca2+-binding sites. Many of said proteins remain unknown or insufficiently characterized. Despite advances in defining Ca2+-dependent activity, considerable experimental difficulties still remain in localizing the protein Ca2+-binding sites [Hadad N. et al.: J. Biol. Chem. 269 (1994) 26864-9]. Fundamental to the understanding of normal and abnormal calcium signaling is the knowledge of the proteins involved in this process. It is therefore an object of this invention to provide a compound binding specifically to Ca2+-binding proteins.
It is an object of this invention to provide a photoreactive azido-ruthenium (AzRu) based probe which specifically binds to Ca2+-binding proteins, and inhibits their activity.
It is another object of this invention to provide an AzRu-based probe which specifically and covalently binds to Ca2+-binding sites of Ca2+-binding proteins, thereby allowing to localize and to characterize such sites.
It is another object of this invention to provide the use of said AzRu-based compound in producing affinity chromatography matrices binding specifically Ca2+-binding proteins, and allowing their purification.
It is still another object of this invention to provide the use of said AzRu-based compound in producing biosensors binding specifically to Ca2+-binding proteins, and allowing their characterization.
It is further an object of this invention to provide diagnostic and therapeutic uses of azido-ruthenium compound associated with defects in the function of Ca2+-binding proteins.